Xyzal (levocetirizine dihydrochloride)

Xyzal is a histamine H1-receptor antagonist indicated for:

• The relief of symptoms associated with seasonal and perennial allergic rhinitis
• The treatment of the uncomplicated skin manifestations of chronic idiopathic urticaria

Seasonal Allergic Rhinitis

Xyzal is indicated for the relief of symptoms associated with seasonal allergic rhinitis in adults and children 2 years of age and older.

Perennial Allergic Rhinitis

Xyzal is indicated for the relief of symptoms associated with perennial allergic rhinitis in adults and children 6 months of age and older.

Chronic Idiopathic Urticaria

Xyzal is indicated for the treatment of the uncomplicated skin manifestations of chronic idiopathic urticaria in adults and children 6 months of age and older.

Use of Xyzal has been associated with somnolence, fatigue, asthenia, and urinary retention.

The most common adverse reactions (rate ≥2% and > placebo) were somnolence, nasopharyngitis, fatigue, dry mouth, and pharyngitis in subjects 12 years of age and older, and pyrexia, somnolence, cough, and epistaxis in children 6 to 12 years of age.

In subjects 1 to 5 years of age, the most common adverse reactions (rate ≥2% and > placebo) were pyrexia, diarrhea, vomiting, and otitis media.

In subjects 6 to 11 months of age, the most common adverse reactions (rate ≥3% and > placebo) were diarrhea and constipation.

In addition to the adverse reactions reported during clinical trials and listed above, adverse events have also been identified during post-approval use of Xyzal. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Adverse events of hypersensitivity and anaphylaxis, increased appetite, angioedema, fixed drug eruption, pruritus, rash and urticaria, convulsion, paraesthesia, dizziness, tremor, dysgeusia, vertigo, movement disorders (including dystonia and oculogyric crisis), aggression and agitation, hallucinations, depression, insomnia, suicidal ideation, visual disturbances, blurred vision, palpitations, tachycardia, dyspnea, nausea, vomiting, hepatitis, dysuria, urinary retention, myalgia, and edema have been reported.

Besides these events reported under treatment with Xyzal, other potentially severe adverse events have been reported from the post-marketing experience with cetirizine. Since levocetirizine is the principal pharmacologically active component of cetirizine, one should take into account the fact that the following adverse events could also potentially occur under treatment with Xyzal: orofacial dyskinesia, severe hypotension, cholestasis, glomerulonephritis, still birth, tic, myoclonus, and extrapyramidal symptoms.

Xyzal is available as 2.5 mg/5 mL (0.5 mg/mL) oral solution and as 5 mg breakable (scored) tablets, allowing for the administration of 2.5 mg, if needed. Xyzal can be taken without regard to food consumption.

Adults and Children 12 Years of Age and Older

The recommended dose of Xyzal is 5 mg (1 tablet or 2 teaspoons [10 mL] oral solution) once daily in the evening. Some patients may be adequately controlled by 2.5 mg (1/2 tablet or 1 teaspoon [5 mL] oral solution) once daily in the evening.

Children 6 to 11 Years of Age

The recommended dose of Xyzal is 2.5 mg (1/2 tablet or 1 teaspoon [5 mL] oral solution) once daily in the evening. The 2.5 mg dose should not be exceeded because the systemic exposure with 5 mg is approximately twice that of adults.

Children 6 months to 5 Years of Age

The recommended initial dose of Xyzal is 1.25 mg (1/2 teaspoon oral solution) [2.5mL] once daily in the evening. The 1.25 mg once daily dose should not be exceeded based on comparable exposure to adults receiving 5 mg.

Dose Adjustment for Renal and Hepatic Impairment

In adults and children 12 years of age and older with:

• Mild renal impairment (creatinine clearance [CLCR] = 50-80 mL/min): a dose of 2.5 mg once daily is recommended;
• Moderate renal impairment (CLCR = 30-50 mL/min): a dose of 2.5 mg once every other day is recommended;
• Severe renal impairment (CLCR = 10-30 mL/min): a dose of 2.5 mg twice weekly (administered once every 3-4 days) is recommended;
• End-stage renal disease patients (CLCR < 10 mL/min) and patients undergoing hemodialysis should not receive Xyzal.

No dose adjustment is needed in patients with solely hepatic impairment. In patients with both hepatic impairment and renal impairment, adjustment of the dose is recommended.

In vitro data indicate that levocetirizine is unlikely to produce pharmacokinetic interactions through inhibition or induction of liver drug-metabolizing enzymes. No in vivo drug-drug interaction studies have been performed with levocetirizine. Drug interaction studies have been performed with racemic cetirizine.

Pharmacokinetic interaction studies performed with racemic cetirizine demonstrated that cetirizine did not interact with antipyrine, pseudoephedrine, erythromycin, azithromycin, ketoconazole, and cimetidine. There was a small decrease (~16%) in the clearance of cetirizine caused by a 400 mg dose of theophylline. It is possible that higher theophylline doses could have a greater effect.

Ritonavir increased the plasma AUC of cetirizine by about 42% accompanied by an increase in half-life (53%) and a decrease in clearance (29%) of cetirizine. The disposition of ritonavir was not altered by concomitant cetirizine administration.

There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Xyzal should be used during pregnancy only if clearly needed.

No peri- and post-natal animal studies have been conducted with levocetirizine. Cetirizine has been reported to be excreted in human breast milk. Because levocetirizine is also expected to be excreted in human milk, use of Xyzal in nursing mothers is not recommended.

Avoid engaging in hazardous occupations requiring complete mental alertness such as driving or operating machinery when taking Xyzal.

Avoid concurrent use of alcohol or other central nervous system depressants with Xyzal.

Use with caution in patients with predisposing factors of urinary retention (e.g. spinal cord lesion, prostatic hyperplasia). Discontinue Xyzal if urinary retention occurs.